The overall objective of the entire project is to study by what mechanism the immunogenicity of organ allografts may be reduced by graft pretreatment -- thereby permitting survival of allogeneic organ grafts. The essential observation here is that mongrel dog kidneys perfused with Concanavalin A (ConA) in vitro and transplanted into allogeneic dogs who receive minimal immunosuppression, survive for prolonged periods of time. The project is therefore designed to (a) study the possible mechanisms by which ConA bounds to organ grafts can lead to prolongation in allogeneic recipients, (b) determine the optimal conditions for the treatment of organ allografts which will permit prolonged allograft survival, (c) investigate how ConA and other modifiers of immunogenicity can alter the immunogenicity of grafts utilizing the mixed lymphocyte culture to simulate immunologic stimulation, (d) apply the lessons learned in the kidney allograft system to organ allografts of liver, intestine, heart and pancreas, and (e) determine the effect on the immunogenicity of organ and tissue allografts of other substances which can be used to pretreat the graft itself. BIBLIOGRAPHIC REFERENCES: Hoffman, R., and Simmons, R.L.: Further studies on the effect of cytochalasin B(CB) on the mitogenic response of human lymphocytes to Concanavalin A (ConA). Fed. proc., 36:1233, 1977. Hoffman, R., Ferguson, R.M., and Simmons, R.L.: Effect of cytochalasin B on human lymphocyte responses to mitogens: Time and concentration dependence. J. Immunol. April, 1977, in press.